反应详情

温度

0 °C

A 12-L, three-neck, round-bottom flask was equipped with an overhead mechanical stirrer, a thermometer and a nitrogen inlet/outlet bubbler. The flask was charged with N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidic chloride (979 g, 2.68 moles), 2, ethylene glycol (1.5 L, 26.8 moles), 4 and tetrahydrofuran (3 L). The stirrer was set to agitate at a moderate rate (to provide a clear red solution) and the mixture was cooled to 0° C. using an ice/water bath. To this cooled solution was added potassium tert-butoxide (362 g, 3.22 moles) over 20 minutes. The reaction mixture was then slowly warmed to room temperature and stirred for a total of 19 hours. A solution of hydrogen chloride in water (8 L, 1M) was introduced into the flask over 10 minutes. The organic fraction was collected and the aqueous fraction was extracted with ethyl acetate (2×4 L). The combined organic fractions were washed with saturated aqueous sodium chloride solution (1×4 L) and the solvents were removed under reduced pressure (30 mm Hg vacuum, final bath temperature at 50° C.) on a rotary evaporator to provide a dark reddish brown oil. This crude organic product was then dissolved with warm (40° C.) methyl tert-butyl ether (2 L) and allowed to cool to room temperature, stirring for a total of 14 hours. The resulting slurry was stirred for 30 minutes at 0° C. after which the precipitate was collected by vacuum filtration and washed with cold methyl tert-butyl ether (1 L). The combined filtrates were concentrated under reduced pressure (30 mmHg vacuum, final bath temperature at 50° C.) on a rotary evaporator to a volume of 500 mL and stirred for 30 minutes at 0° C. The resulting precipitate was collected by vacuum filtration and washed with cold methyl tert-butyl ether (200 mL). Two crops of solid product were then combined and dried overnight (30 mm Hg, 40° C.) to produce 2-hydroxyethyl-N,N,N′,N′-tetrakis(2-chloroethyl)phosphorodiamidate, 3, as a tan powder (526 gm, 50% yield). TLC analysis showed one spot (Rf0.62; methanol:chloroform 1:9). Melting point: 76-78° C.; IR (KBr) 3372, 2957, 1459, 1344, 1206, 1098, 1053, 929 cm−1; MS (CI, methane) m/z 391(MH+), 353, 339, 248, 106. A thermal analysis (DSC) showed two exothermic decomposition ranges of 164-179 and 222-231 C.

1. customto provide a clear red solution) and the mixture
2. temperatureThe reaction mixture was then slowly warmed to room temperature
3. stirringstirred for a total of 19 hours
4. customThe organic fraction was collected
5. extractionthe aqueous fraction was extracted with ethyl acetate (2×4 L)
6. washThe combined organic fractions were washed with saturated aqueous sodium chloride solution (1×4 L)
7. customthe solvents were removed under reduced pressure (30 mm Hg vacuum
8. customfinal bath temperature at 50° C.) on a rotary evaporator
9. customto provide a dark reddish brown oil
10. dissolutionThis crude organic product was then dissolved
11. temperatureto cool to room temperature
12. stirringstirring for a total of 14 hours
13. stirringThe resulting slurry was stirred for 30 minutes at 0° C. after which the precipitate
14. filtrationwas collected by vacuum filtration
15. washwashed with cold methyl tert-butyl ether (1 L)
16. concentrationThe combined filtrates were concentrated under reduced pressure (30 mmHg vacuum
17. customfinal bath temperature at 50° C.) on a rotary evaporator to a volume of 500 mL
18. stirringstirred for 30 minutes at 0° C
19. filtrationThe resulting precipitate was collected by vacuum filtration
20. washwashed with cold methyl tert-butyl ether (200 mL)
21. customdried overnight (30 mm Hg, 40° C.)